BACELL HEALTH Résumé de rapport

While bacteria remain one of the main threats to human health and well-being, particularly in the light of increasing resistance to antimicrobials, they also have the capacity to provide products (e.g. antibiotics, vaccines and biotherapeutics) that have a positive influence on human health. Thus, bacteria are both targets for, and producers of, biopharmaceuticals.

BACELL HEALTH was a research and technological development project that aimed to address both the negative and positive characteristics of bacterial behaviour by undertaking an integrated and in-depth study of the response of Gram-positive bacteria to stresses encountered by pathogens during infection and by industrially important strains during bio-processes. Although both of these environments induce generic stress responses, they also induce non-overlapping specific stress responses (e.g. pH, iron and oxidative stress in the case of macrophages, protein synthesis, secretion and nutrient stress in the case of industrial fermentations). The ability of bacteria to detect, respond to and resist environmental insult is a key element in their survival and productivity.

BACELL HEALTH aimed to develop a profound understanding of the integrative cell management and associated stress resistance processes that are essential for sustaining bacteria as effective pathogens, or as efficient producers of pharmaceutically-active proteins. The major challenge was to understand how individual regulatory pathways are networked to maintain cellular homeostasis. This network was referred to as the 'Cell stress management system'. The knowledge obtained was used to model the regulatory networks that comprise the Cell stress management system, identifying key targets for the development of novel anti-infectives and bottlenecks that limit the productivity of Bacillus for the production of biopharmaceuticals.

BACELL HEALTH was proposed to build on the technological knowledge and industrial base established in Europe by focusing on aspects that directly influence human health, namely the development of anti-infective agents and the improved production of pharmaceutically-active proteins. The added-value nature of this project was confirmed not only by the full participation of three European companies, but also by the support of the Bacillus industrial platform (BACIP). Expected deliverables included knowledge of fundamental biological systems, the identification of novel targets for the development of broad-spectrum and / or Gram-selective anti-infectives, an improved understanding of microbial virulence and the regulatory response of bacteria to host-mediated stress responses, prototypes of production strains and new protein structures and functions. In addition, the consortium was expected to add to the stock of highly trained young European scientists, and has disseminated knowledge via workshops and practical training courses.

European research groups and industries are global leaders in the development of Bacillus technology and the commercial exploitation of bacilli. A direct industrial benefit of BACELL HEALTH is therefore to help maintain Europe's competitive market position in the face of competition from the United States and the Far East. The importance of this work for industry is also reflected by the participation of three industrial partners in this project. All three of these use Bacillus species for production purposes. The project has impacted on human health by providing knowledge of the mechanisms which bacteria use to avoid the immune response.

In addition to improved production strains and improved production strategies, the current project has also resulted in the identification of key genes for virulence traits in certain Gram-positive pathogens. This provides leads toward the identification of novel drug targets and, finally, the production of novel anti-infectives.

At least three patent applications are likely to emerge from this work, which will be filed by partners in the project. In addition, more than 140 publications will appear in the international, peer-reviewed, scientific literature. About 40 % of these are directly based on the results from this project, whereas the remainder is indirectly linked to the work in this project.

During the contract period, consortium members have presented more than 150 oral presentations or posters at national and international scientific meetings, on results which are directly or indirectly related to the project.